In Reply: We agree with Dr Choi and colleagues
that direct comparisons within active control clinical trials are the optimal
method of assessing differences between drugs. When the absence of active
control data makes the use of indirect comparisons necessary, it is important
to compare things that are similar.

Their reference to MRFIT1 is surprising
on several counts. First, they make an indirect comparison between hydrochlorothiazide
and chlorthalidone even though the choice between the 2 diuretics was a local
option and not a part of the randomized design. Second, for the randomized
comparison between special intervention and usual care, MRFIT, which did not
use a factorial design, has not generally been included in meta-analyses of
hypertension trials2 because the effects of
antihypertensive treatment cannot be separated from the effects of the MRFIT
nutrition and smoking interventions. Finally, high-dose diuretics were used
in MRFIT. These differ from low-dose diuretics in their effects on CHD2,3 and are generally no longer used or
recommended in clinical practice. For these reasons, our meta-analysis focused
only on trials that evaluated low-dose diuretic therapies. Both ALLHAT and
the Second Australian National Blood Pressure Trial did use low-dose diuretic
therapies.4,5 ALLHAT included
a large proportion of African Americans. Among European Americans in ALLHAT,
the differences in outcomes between lisinopril and chlorthalidone were minor.4